The Brain and its Vasculature represents the continuation of a 35-year study of the vasculature of the human brain and its relationship to brain function in health and disease. Because of the intimate relationship between brain function and the brain vasculature that has been uncovered by ourselves and others, studies of the vascular and metabolic responses to functionally-induced changes in neuronal activity provide a unique window into the functional organization of the human brain. Pursuit of this opportunity was greatly enhanced by the development of functional imaging techniques beginning in the 1970's with positron emission tomography (PET) which was pioneered in our laboratory with substantial support from this program project. This work has now been extended the magnetic resonance imaging (MRI) where it has expanded dramatically both in its sophistication and wide spread use. This competing renewal application carries forward many of the long standing interests and strengths of this program project. Stimulated by findings during the current grant period we now propose to examine more closely the relationship between brain blood flow and oxygen consumption as expressed in the oxygen extraction fraction (OEF). In this Project we will examine the hypothesis that the OEF can be used to define a baseline state of establishment of a baseline for a given area of the cerebral cortex. In Project we take advantage of what we have already learned from this approach. Using the OEF as a means of establishing a baseline level of activity we have identified areas along the anterior and posterior midline of the cerebral hemispheres whose activity is significantly higher than brain as a whole. Activity in these areas routinely declines with the onset of focused cognitive activity. This decline can, however, be attenuated by emotional arousal. Taken together with extant observations from others leads us to hypothesize the existence of a default system in cerebral cortex designed to assemble and evaluate information, both external and internal, of broad general relevance to the welfare of the individual. This system is an important determinant of our emotional and motivational state. Experiments are designed to test this hypothesis. In this Project we continue one of the major long standing strengths of this program project, the study of language instantiation in the human brain. New to the current proposal is the application of our knowledge and strategies to the study of language recovery in stroke patients. While seemingly different than the first two projects, one Project does, indeed, benefit through specific interactions with another Project and both the MR and Image Analysis Cores. Together the work in this program project captures the efforts of a tightly nit group of investigators who have worked closely together sharing common interest and techniques. The result has been a program with a long-standing record of success.